The overall goal of this proposal is to better define and understand the phenomenon of natural killing in humans and its possible in vivo relevance. The work will focus onthe mechanisms by which biological response modifiers such as interferon, poly I:C, and metabolites of the arachidonic acid pathway modulate NK activity in vitro on a single cell level. The effect of lymphoblastoid interferon (mainly AlphaIFN) treatment of cancer patients on NK level will also be assessed and compared with clinical findings. To determine the physical and chemical nature of binding and selectivity of NK cells we will employ innovative binding methodology and membrane fractionation procedures. We propose to develop monoclonal antibodies specific to NK surface markers as possible tools to isolate and identify NK cells. Furthermore, we propose to establish human NK-like cell lines to be used as a homogeneous source of effector cells. Our long-term goals, therefore, are to investigate the mechanisms involved in NK regulation and killing which will be of great theoretical and therapeutical importance for the eventual manipulation of the host defense against cancer.